Entry
Name
Shigellosis - Homo sapiens (human)
Description
Shigellosis, or bacillary dysentery, is an intestinal infection caused by Shigella, a genus of enterobacteria. Shigella are potential food-borne pathogens that are capable of colonizing the intestinal epithelium by exploiting epithelial-cell functions and circumventing the host innate immune response. During basolateral entry into the host-cell cytoplasm, Shigella deliver a subset of effectors into the host cells through the type III secretion system. The effectors induce membrane ruffling through the stimulation of the Rac1-WAVE-Arp2/3 pathway, enabling bacterial entry into the epithelial cells. During multiplication within the cells, Shigella secrete another subset of effectors. VirG induces actin polymerization at one pole of the bacteria, allowing the bacteria to spread intracellularly and to infect adjacent cells. OspF, OspG and IpaH(9.8) downregulate the production of proinflammatory cytokines such as IL-8, helping bacteria circumvent the innate immune response.
Class
Human Diseases; Infectious disease: bacterial
BRITE hierarchy
Pathway map
Network
Element
N00927 Escherichia/Shigella NleE/OspZ to TNF-NFKB signaling pathway
N00941 Shigella IpaH9.8 to NOD-NFKB signaling pathway
N00942 Shigella OspG to TNF-NFKB signaling pathway
N00943 Shigella IpaH4.5 to TNF-NFKB signaling pathway
N00944 Shigella OspI to TNF-NFKB signaling pathway
N00945 Shigella IpaH1.4/2.5 to TNF-NFKB signaling pathway
N00946 Shigella IpaJ to cGAS-STING signaling pathway
N00947 Shigella Ipa4.5 to cGAS-STING signaling pathway
N00948 Shigella IpaH7.8 to NLRP3 Inflammasome signaling pathway
N00949 Shigella IpaB to NLRC4 Inflammasome signaling pathway
N00950 Shigella FimA to crosstalk between extrinsic and intrinsic apoptotic pathways
N00952 Shigella IpgB1 to ITGA/B-RHOG-RAC signaling pathway
N01067 Shigella IpgD to ARNO-ARF-ACTB_G signaling pathway
N01069 Shigella IpgB1 to ITGA/B-FAK-RAC signaling pathway
N01071 Shigella IpgB1 to ITGA/B-FAK-CDC42 signaling pathway
N01073 Shigella IpgB2 to ITGA/B-RhoGEF-RhoA signaling pathway
N01074 Shigella IpaA to ITGA/B-RhoGEF-RhoA signaling pathway
N01075 Shigella IcsB to ITGA/B-RhoGEF-RhoA signaling pathway
N01076 Shigella IcsB to ITGA/B-FAK-CDC42 signaling pathway
N01077 Shigella IcsB to ITGA/B-FAK-RAC signaling pathway
N01079 Shigella IpaC to Actin signaling pathway
N01081 Shigella IpaB/C/D to ITGA/B-TALIN/VINCULIN signaling pathway
N01082 Shigella IpaA to ITGA/B-TALIN/VINCULIN signaling pathway
N01083 Shigella OspE to ITGA/B-TALIN/VINCULIN signaling pathway
N01283 Shigella OspF to TLR2/4-MAPK signaling pathway
N01284 Shigella IcsP to Autophagy-vesicle elongation
Disease
H00299 Shigellosis; Bacillary dysentery
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
10092 ARPC5; actin related protein 2/3 complex subunit 5 [KO:K05754 ]
10093 ARPC4; actin related protein 2/3 complex subunit 4 [KO:K05755 ]
10094 ARPC3; actin related protein 2/3 complex subunit 3 [KO:K05756 ]
10095 ARPC1B; actin related protein 2/3 complex subunit 1B [KO:K05757 ]
10109 ARPC2; actin related protein 2/3 complex subunit 2 [KO:K05758 ]
10241 CALCOCO2; calcium binding and coiled-coil domain 2 [KO:K21348 ]
102724594 U2AF1L5; U2 small nuclear RNA auxiliary factor 1 like 5 [KO:K12836 ]
10392 NOD1; nucleotide binding oligomerization domain containing 1 [KO:K08727 ]
10454 TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403 ]
10552 ARPC1A; actin related protein 2/3 complex subunit 1A [KO:K05757 ]
10892 MALT1; MALT1 paracaspase [KO:K07369 ] [EC:3.4.22.-]
11146 GLMN; glomulin, FKBP associated protein [KO:K23345 ]
114548 NLRP3; NLR family pyrin domain containing 3 [KO:K12800 ]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467 ] [EC:2.7.11.10 ]
1398 CRK; CRK proto-oncogene, adaptor protein [KO:K04438 ]
1399 CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438 ]
1437 CSF2; colony stimulating factor 2 [KO:K05427 ]
1729 DIAPH1; diaphanous related formin 1 [KO:K05740 ]
1793 DOCK1; dedicator of cytokinesis 1 [KO:K13708 ]
199746 U2AF1L4; U2 small nuclear RNA auxiliary factor 1 like 4 [KO:K12836 ]
23118 TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404 ]
23291 FBXW11; F-box and WD repeat domain containing 11 [KO:K03362 ]
257397 TAB3; TGF-beta activated kinase 1 (MAP3K7) binding protein 3 [KO:K12793 ]
25851 TECPR1; tectonin beta-propeller repeat containing 1 [KO:K17988 ]
26100 WIPI2; WD repeat domain, phosphoinositide interacting 2 [KO:K17908 ]
29108 PYCARD; PYD and CARD domain containing [KO:K12799 ]
3059 HCLS1; hematopoietic cell-specific Lyn substrate 1 [KO:K06106 ]
340061 STING1; stimulator of interferon response cGAMP interactor 1 [KO:K12654 ]
3554 IL1R1; interleukin 1 receptor type 1 [KO:K04386 ]
3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030 ]
3661 IRF3; interferon regulatory factor 3 [KO:K05411 ]
3708 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
3709 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
3710 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
387 RHOA; ras homolog family member A [KO:K04513 ]
392288 MAP1LC3BP1; microtubule associated protein 1 light chain 3 beta pseudogene 1 [KO:K10435 ]
440738 MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435 ]
4615 MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729 ]
4671 NAIP; NLR family apoptosis inhibitory protein [KO:K12807 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
54874 FNBP1L; formin binding protein 1 like [KO:K20121 ]
55062 WIPI1; WD repeat domain, phosphoinositide interacting 1 [KO:K17908 ]
57521 RPTOR; regulatory associated protein of MTOR complex 1 [KO:K07204 ]
581 BAX; BCL2 associated X, apoptosis regulator [KO:K02159 ]
58484 NLRC4; NLR family CARD domain containing 4 [KO:K12805 ]
596 BCL2; BCL2 apoptosis regulator [KO:K02161 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
6352 CCL5; C-C motif chemokine ligand 5 [KO:K12499 ]
63916 ELMO2; engulfment and cell motility 2 [KO:K18985 ]
643246 MAP1LC3B2; microtubule associated protein 1 light chain 3 beta 2 [KO:K10435 ]
6500 SKP1; S-phase kinase associated protein 1 [KO:K03094 ]
664 BNIP3; BCL2 interacting protein 3 [KO:K15464 ]
7132 TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158 ]
7188 TRAF5; TNF receptor associated factor 5 [KO:K09849 ]
7307 U2AF1; U2 small nuclear RNA auxiliary factor 1 [KO:K12836 ]
7311 UBA52; ubiquitin A-52 residue ribosomal protein fusion product 1 [KO:K02927 ]
7335 UBE2V1; ubiquitin conjugating enzyme E2 V1 [KO:K10704 ]
7336 UBE2V2; ubiquitin conjugating enzyme E2 V2 [KO:K10704 ]
7416 VDAC1; voltage dependent anion channel 1 [KO:K05862 ]
81631 MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435 ]
81858 SHARPIN; SHANK associated RH domain interactor [KO:K20894 ]
81873 ARPC5L; actin related protein 2/3 complex subunit 5 like [KO:K05754 ]
826 CAPNS1; calpain small subunit 1 [KO:K08583 ]
8290 H3-4; H3.4 histone, cluster member [KO:K11253 ]
84557 MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210 ]
8717 TRADD; TNFRSF1A associated via death domain [KO:K03171 ]
8915 BCL10; BCL10 immune signaling adaptor [KO:K07368 ]
8945 BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362 ]
8976 WASL; WASP like actin nucleation promoting factor [KO:K23612 ]
9181 ARHGEF2; Rho/Rac guanine nucleotide exchange factor 2 [KO:K12791 ]
92610 TIFA; TRAF interacting protein with forkhead associated domain [KO:K23826 ]
9564 BCAR1; BCAR1 scaffold protein, Cas family member [KO:K05726 ]
960 CD44; CD44 molecule (IN blood group) [KO:K06256 ]
9844 ELMO1; engulfment and cell motility 1 [KO:K12366 ]
998 CDC42; cell division cycle 42 [KO:K04393 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C04549 1-Phosphatidyl-1D-myo-inositol 3-phosphate
C04637 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C04737 alpha-D-Galactosyl-(1->4)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
C05981 Phosphatidylinositol-3,4,5-trisphosphate
C11472 D-glycero-beta-D-manno-Heptose 1,7-bisphosphate
C11557 1-Phosphatidyl-1D-myo-inositol 5-phosphate
Reference
Authors
Schnupf P, Sansonetti PJ
Title
Shigella Pathogenesis: New Insights through Advanced Methodologies.
Journal
Reference
Authors
Mattock E, Blocker AJ
Title
How Do the Virulence Factors of Shigella Work Together to Cause Disease?
Journal
Reference
Authors
Ashida H, Mimuro H, Sasakawa C
Title
Shigella manipulates host immune responses by delivering effector proteins with specific roles.
Journal
Reference
Authors
Sasakawa C
Title
A new paradigm of bacteria-gut interplay brought through the study of Shigella.
Journal
Reference
Authors
Ashida H, Kim M, Sasakawa C
Title
Manipulation of the host cell death pathway by Shigella.
Journal
Reference
Authors
Siqueira MDS, Ribeiro RM, Travassos LH
Title
Autophagy and Its Interaction With Intracellular Bacterial Pathogens.
Journal
Reference
Authors
Pinaud L, Sansonetti PJ, Phalipon A
Title
Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors.
Journal
Related pathway
hsa04621 NOD-like receptor signaling pathway
hsa04810 Regulation of actin cytoskeleton
KO pathway